Light-based treatments (i.e., phototherapy) of many kinds are being used or considered for addressing a number of medical ailments. Phototherapy of diseased tissue includes various forms of treatment including photoablation, photodynamic therapy, or photocoagulation. In each of these, control of the treatment outcome relies on control of the dosage of light administered, as well as the dosage of any additional agents such as photosensitizers used in conjunction with the therapeutic light. Accurate measurement and monitoring of administered light dosage (i.e., dosimetry) is essential for comprehensive control of the process and preferably is available simultaneously with the application of the therapeutic light. Further, correct interpretations of dosimetric data are only possible within the context of an inclusive understanding of the relevant optical properties of the target tissue.
Photodynamic therapy (PDT) is an evolving treatment that employs the interaction between photoactive drugs and light of an appropriate wavelength to destroy diseased or malignant tissue. During a PDT procedure, one or more photosensitive molecules are administered within a target tissue of a patient and are then illuminated with phototherapeutic light having a wavelength operable for interacting with the photosensitive molecules in such a manner as to produce a photoactivated species of the molecules possessing molecules in such a manner as to produce a photoactivated species of the molecules possessing therapeutic properties. The photoactivated species that are formed either destroy cells or arrest physiological activity in the associated diseased tissue thereby effecting a treatment of the target tissue.
A problem associated with administering phototherapy in general, and photodynamic therapy in particular, is accurate dosimetry; that is, establishing when an effective dose of light has been administered to cure the diseased target tissue. For example, the amount of photodynamic therapy administered to a target tissue depends on the number of photoactivated species produced which, in turn, depends upon both the amount or concentration of photosensitizer accumulated within the tissue as well as the amount of light delivered to the photosensitizer. Thus, the photosensitive reaction, which is responsible for the therapeutic effects sought, is a second order reaction. In other words, the rate of formation of photoactivated therapeutic species within a target tissue undergoing phototherapy is proportional to both the intensity of light reaching the tissue and the concentration of photosensitive or photoreactive molecules within the diseased target tissue. Inaccurate light dosimetry can lead to either incomplete treatment of the diseased tissue, resulting in recurrence, or to significant damage to healthy tissue surrounding the diseased tissue. Accordingly, safe and effective application of photodynamic therapy requires accurate and adequate light delivery together with careful monitoring of the phototherapy irradiation.
Within a three-dimensional target tissue matrix, accurate monitoring of light dosage requires careful control of the positioning of the dosimetry fiber in order to yield accurate and reliable information, as the intensity of light fluence (i.e., irradiance) varies with the distance from the light source. The amount of therapeutic light delivered to the target tissue is, in general, inversely proportional to the square of the distance of the light source from the target tissue. That is, excluding light loss due to absorption or scattering of therapeutic light by non-target intervening media, the intensity of treatment light reaching a target tissue is inversely proportional to the square of the distance between the emission point of the light source and the target tissue. Due to relative uncertainty in the distance between a source of light (such as a light diffuser element) and the target tissue undergoing treatment, the quadratic reduction in the intensity of light reaching a target tissue with respect to the distance between the source of light and target tissue makes it difficult to establish the precise amount of light administered to a target tissue during phototherapy.
Another important factor in correctly monitoring and measuring the distribution of light are the specific optical properties of the target tissue. In order to reliably determine these optical properties, it is generally necessary to obtain a plurality of irradiance measurements, each taken at a unique and accurately known distance from the light source. In order to achieve this with existing technology, multiple fiber optic dosimetry probes are required, each individually and carefully placed within the target tissue.
Previously, fiber optic devices of many forms have been used for delivering light in medical treatments and therapies. Similar devices have also been used to gather dosimetric data from treatment sites. Conventionally, these light delivery and irradiance measurement devices have been separate units and have been brought together in cases where monitoring of light treatment has been desired. For example, a typical prior art method involves the insertion of an optical fiber to deliver light to the target tissue. Another optical fiber is inserted, typically via a different entry point, and used as a light detecting probe. In order to determine the light fluence distribution throughout the target tissue, measurements are made at several insertion points and/or at several insertion angles. The multiple insertion points and tracks must be measured and recorded in order to later calculate the distance from the end of the light delivery optical fiber and the light detecting probe at each measurement location. This method is unsuitable for a number of applications, for example when access to the target tissue is restricted.
In another prior art method, a light delivery and a light detector fiber are inserted into a sheath. During the treatment process, the light detector fiber may then be withdrawn in discrete steps, for example using a vernier stage, to allow light intensity readings to be made at different interfiber separation distances. This prior art method involves the use of a light delivery fiber and a single light detector fiber placed interstitially via a single point of entry in contrast to the other conventional method employing two separate systems, one for delivery of light, and the other(s) for detection of light penetration.
These prior art techniques suffer from significant disadvantages in addition to those previously mentioned. For example, they require time to adjust the placement of the detection fibers. The speed with which the light treatment may be applied and measured is important to reduce complications. Also, obtaining accurate placement of the detection fibers is difficult. Additionally, with prior art techniques there is need to accurately calculate the distance between the ends of the light delivery and light detection optical fibers.
Accordingly, there is a continuing need for an improved dosimetry probe adapted to sample the light incident upon a diseased target tissue undergoing phototherapy. Desirably, the dosimetry probe would monitor the photoactivation process in real-time so that the phototherapy process can be controlled and optimized for each individual application. A preferred probe would allow irradiance and light penetration measurements to be taken in-situ at precise displacement locations to determine the extent to which light penetrates the target tissue and allow the optical properties of the target tissue to be determined. It would also be desirable to combine the capabilities of light delivery, real-time dosimetry and measurement of the optical properties of target tissue into a single, easy-to-use probe.